JP2017522350A5 - - Google Patents
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- JP2017522350A5 JP2017522350A5 JP2017505234A JP2017505234A JP2017522350A5 JP 2017522350 A5 JP2017522350 A5 JP 2017522350A5 JP 2017505234 A JP2017505234 A JP 2017505234A JP 2017505234 A JP2017505234 A JP 2017505234A JP 2017522350 A5 JP2017522350 A5 JP 2017522350A5
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- 150000001875 compounds Chemical class 0.000 claims 12
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 6
- 239000011780 sodium chloride Substances 0.000 claims 6
- 201000003883 cystic fibrosis Diseases 0.000 claims 5
- 239000003112 inhibitor Substances 0.000 claims 4
- 230000002401 inhibitory effect Effects 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 208000002815 Pulmonary Hypertension Diseases 0.000 claims 3
- 206010069351 Acute lung injury Diseases 0.000 claims 2
- 206010018651 Graft versus host disease Diseases 0.000 claims 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 2
- 201000009267 bronchiectasis Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 230000004054 inflammatory process Effects 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- YKRWCOVMFLQPQJ-UHFFFAOYSA-N 2-(2-chlorophenyl)oxetane Chemical compound ClC1=CC=CC=C1C1OCC1 YKRWCOVMFLQPQJ-UHFFFAOYSA-N 0.000 claims 1
- XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 claims 1
- 229940005497 ANTICHOLINERGIC AGENTS Drugs 0.000 claims 1
- 208000002223 Abdominal Aortic Aneurysm Diseases 0.000 claims 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 1
- 108010022043 Antineutrophil Cytoplasmic Antibodies Proteins 0.000 claims 1
- 208000007474 Aortic Aneurysm Diseases 0.000 claims 1
- 208000006673 Asthma Diseases 0.000 claims 1
- 210000000621 Bronchi Anatomy 0.000 claims 1
- 102000003902 Cathepsin C Human genes 0.000 claims 1
- 108090000267 Cathepsin C Proteins 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 229940064701 Corticosteroid nasal preparations for topical use Drugs 0.000 claims 1
- 229960001334 Corticosteroids Drugs 0.000 claims 1
- 206010070976 Craniocerebral injury Diseases 0.000 claims 1
- 206010012601 Diabetes mellitus Diseases 0.000 claims 1
- 229940121647 EGFR inhibitors Drugs 0.000 claims 1
- 206010014561 Emphysema Diseases 0.000 claims 1
- 206010052828 Eosinophilic disease Diseases 0.000 claims 1
- 208000004930 Fatty Liver Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 102000000543 Histamine receptors Human genes 0.000 claims 1
- 108010002059 Histamine receptors Proteins 0.000 claims 1
- 206010022489 Insulin resistance Diseases 0.000 claims 1
- YEESKJGWJFYOOK-IJHYULJSSA-N Leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 102100007288 PTGDR2 Human genes 0.000 claims 1
- 101710013017 PTGDR2 Proteins 0.000 claims 1
- 206010039073 Rheumatoid arthritis Diseases 0.000 claims 1
- 208000005765 Traumatic Brain Injury Diseases 0.000 claims 1
- 206010047115 Vasculitis Diseases 0.000 claims 1
- 239000000808 adrenergic beta-agonist Substances 0.000 claims 1
- 201000005794 allergic hypersensitivity disease Diseases 0.000 claims 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 1
- 230000003042 antagnostic Effects 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 244000052616 bacterial pathogens Species 0.000 claims 1
- 230000003454 betamimetic Effects 0.000 claims 1
- 239000000812 cholinergic antagonist Substances 0.000 claims 1
- 230000001684 chronic Effects 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 201000009910 diseases by infectious agent Diseases 0.000 claims 1
- 230000003176 fibrotic Effects 0.000 claims 1
- 230000002496 gastric Effects 0.000 claims 1
- 201000009794 idiopathic pulmonary fibrosis Diseases 0.000 claims 1
- 200000000018 inflammatory disease Diseases 0.000 claims 1
- 239000003591 leukocyte elastase inhibitor Substances 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000003448 neutrophilic Effects 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000002685 pulmonary Effects 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000001225 therapeutic Effects 0.000 claims 1
- 229940083878 topical for treatment of hemorrhoids and anal fissures Corticosteroids Drugs 0.000 claims 1
- 0 *C(C(C(CCC1)=O)=C1N1*)N(*)C1=O Chemical compound *C(C(C(CCC1)=O)=C1N1*)N(*)C1=O 0.000 description 1
Claims (13)
- 下記式1
(式中、
R1は、CNで置換され、かつ
第2の置換基R1.1で置換されたフェニルであり、
R1.1は、-SO2-CH3、-SO-CH3、-CH2-OH、-SO2-CH2CH2-OH、-SO2-CH2CH2-OCH3及び-SO2-CH2CH2CH2-OHから成る群より選択され、
R2は、CF3で置換されたフェニルであり、
R3は、H、CH3、-CO-NH-CH3、-CH2CH2-OH及び-CH2-オキセタンから成る群より選択される）
の化合物又はその医薬的に許容できる塩
（但し、式1の化合物は、下記化合物
- R1が、CNで置換され、かつ
第2の置換基R1.1で置換されたフェニルであり、
R1.1が、-SO2-CH3、-SO-CH3及び-SO2-CH2CH2-OHから成る群より選択され、
R2が、CF3で置換されたフェニルであり、
R3が、H、CH3及び-CH2CH2-OHから成る群より選択される、
請求項1に記載の式1の化合物又はその医薬的に許容できる塩。 - R1.1が-SO2-CH3である、
請求項1又は2に記載の式1の化合物又はその医薬的に許容できる塩。 - R1.1が-SO-CH3である、
請求項1又は2に記載の式1の化合物又はその医薬的に許容できる塩。 - 下記化合物1.a〜1.d
請求項1に記載の式1の化合物。 - 式1の立体配置が下記式1'である、
請求項1〜5のいずれか1項に記載の化合物又はその医薬的に許容できる塩。 - 請求項1〜6のいずれか1項に記載の式1の1種以上の化合物又はその医薬的に活性な塩を含有することを特徴とする医薬組成物。
- 喘息、アレルギー性疾患、胃腸の炎症性疾患、糸球体腎炎、好酸球性疾患、慢性閉塞性肺疾患、病原微生物による感染症又は関節リウマチの治療のための請求項７に記載の医薬組成物。
- 好中球性疾患、嚢胞性線維症(CF)、非嚢胞性線維症、特発性肺線維症、気管支拡張症、ANCA関連血管炎、肺癌、非嚢胞性線維性気管支拡張症、肺気腫、慢性気管支炎、急性肺傷害(ALI)、急性呼吸促迫症候群(ARDS)、肺高血圧症、肺動脈性肺高血圧症(PAH)又はα1-アンチトリプシン欠乏症(AATD.)の治療のための請求項７に記載の医薬組成物。
- 肥満症もしくは関連炎症、インスリン抵抗性、糖尿病、脂肪肝又は肝脂肪過多症の治療のための請求項７に記載の医薬組成物。
- 外傷性脳損傷、腹部大動脈瘤又は移植片対宿主病(GvHD)の治療のための請求項７に記載の医薬組成物。
- 好中球エラスターゼ阻害薬が治療利益を有する疾患の治療又は予防ための請求項７に記載の医薬組成物であって、治療的又は予防的に有効な量の請求項1〜6のいずれか1項に記載の式1の化合物を含む前記医薬組成物。
- 請求項1〜6のいずれか1項に記載の式1の化合物に加えて、ベータミメティック、抗コリン薬、コルチコステロイド、PDE4阻害薬、LTD4拮抗薬、EGFR阻害薬、カテプシンC阻害薬、CRTH2阻害薬、5-LO阻害薬、ヒスタミン受容体拮抗薬及びSYK阻害薬から成る群より選択される医薬的に活性な化合物、又は2若しくは3種の活性物質の組合せを含む医薬組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14179261.4 | 2014-07-31 | ||
| EP14179261 | 2014-07-31 | ||
| PCT/EP2015/067506 WO2016016368A1 (en) | 2014-07-31 | 2015-07-30 | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017522350A JP2017522350A (ja) | 2017-08-10 |
| JP2017522350A5 true JP2017522350A5 (ja) | 2018-07-26 |
| JP6484327B2 JP6484327B2 (ja) | 2019-03-13 |
Family
ID=51257368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017505234A Active JP6484327B2 (ja) | 2014-07-31 | 2015-07-30 | 置換二環式ジヒドロピリミジノン及び好中球エラスターゼ活性の阻害薬としてのそれらの使用 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US9440930B2 (ja) |
| EP (1) | EP3174862B1 (ja) |
| JP (1) | JP6484327B2 (ja) |
| WO (1) | WO2016016368A1 (ja) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE47493E1 (en) | 2014-02-20 | 2019-07-09 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9856232B1 (en) | 2017-06-20 | 2018-01-02 | King Saud University | Dihydropyrimidinone derivatives |
| US10047071B1 (en) | 2018-01-15 | 2018-08-14 | King Saud University | Dihydropyrimidinone derivatives |
| US10111873B1 (en) | 2018-01-17 | 2018-10-30 | King Saud University | Dihydropyrimidinone derivatives |
| EP4031138A1 (en) | 2019-09-17 | 2022-07-27 | Mereo Biopharma 4 Limited | Alvelestat for use in the treatment of graft rejection, bronchiolitis obliterans syndrome and graft versus host disease |
| MX2022012942A (es) | 2020-04-16 | 2023-01-11 | Mereo Biopharma 4 Ltd | Metodos que involucran el inhibidor de la elastasa de neutrofilo alvelestat para el tratamiento de enfermedades respiratorias mediadas por deficiencia de alfa-1 antitripsina. |
| IL312002A (en) | 2021-10-20 | 2024-06-01 | Mereo Biopharma 4 Ltd | Neutrophil elastase inhibitors for use in the treatment of fibrosis |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2271365T3 (es) | 2001-12-20 | 2007-04-16 | Bayer Healthcare Ag | Derivados de 1,4-dihidro-1,4-difenilpiridina. |
| CA2496815C (en) | 2002-08-27 | 2011-04-26 | Bayer Healthcare Ag | Dihydropyridinone derivatives |
| GB0219896D0 (en) | 2002-08-27 | 2002-10-02 | Bayer Ag | Dihydropyridine derivatives |
| KR20050042190A (ko) | 2002-09-10 | 2005-05-04 | 바이엘 헬스케어 아게 | 급성 및 만성 염증성, 허혈성 및 재형성 과정에 대한 치료제로서의 피리미디논 유도체 |
| GB2392910A (en) * | 2002-09-10 | 2004-03-17 | Bayer Ag | 2-Oxopyrimidine derivatives and their use as human leukocyte elastase inhibitors |
| EP1539710B1 (en) | 2002-09-10 | 2010-10-27 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclic derivatives |
| US7893073B2 (en) | 2004-02-26 | 2011-02-22 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclic derivatives |
| EP1723121B1 (en) | 2004-02-26 | 2012-07-25 | Bayer Pharma Aktiengesellschaft | 1,4-diaryl-dihydropyrimidin-2-ones and their use as human neutrophil elastase inhibitors |
| GB0502258D0 (en) | 2005-02-03 | 2005-03-09 | Argenta Discovery Ltd | Compounds and their use |
| GB0512940D0 (en) | 2005-06-24 | 2005-08-03 | Argenta Discovery Ltd | Compounds and their use |
| US8198288B2 (en) | 2006-05-04 | 2012-06-12 | Pulmagen Therapeutics (Inflammation) Limited | Tetrahydropyrrolopyrimidinediones and their use in therapy |
| WO2009013444A1 (en) | 2007-07-25 | 2009-01-29 | Argenta Discovery Limited | Tetrahydropyrrolopyrimidinediones and their use as human neutrophil elastase inhibitors |
| PT2024367E (pt) | 2006-05-04 | 2010-12-03 | Pulmagen Therapeutics Inflammation Ltd | Tetra-hidropirrolopirimidinadionas e a sua utilização a título de inibidores da elastase de neutrófilos humana |
| DE102006031314A1 (de) | 2006-07-01 | 2008-01-03 | Bayer Healthcare Aktiengesellschaft | Verwendung von 1,4-Diaryl-dihydropyrimidin-2-on-Derivaten zur Behandlung der pulmonalen arteriellen Hyptertonie |
| US20100010024A1 (en) | 2006-07-01 | 2010-01-14 | Bayer Healthcare Ag | Use of1,4-diaryl-dihydropyrimidine-2-on derivatives for treating pulmonary arterial hypertension |
| WO2009037413A1 (en) | 2007-09-19 | 2009-03-26 | Argenta Discovery Limited | Dimers of 5- [ (4-cyanophenyl) sulfinyl] -6-methyl-2-oxo-1- [3- (trifluoromethyl)phenyl] -1,2-dihydropyridine-3-carboxamide as inhibitors of human neutrophil elastase for treating respiratory diseases |
| WO2009060158A1 (en) | 2007-11-07 | 2009-05-14 | Argenta Discovery Limited | 4- (4-cyanophenyl) -1- (3-trifluoromethylphenyl) -3,4, 6, 7-tetrahydro-1h-pyrrolo [3, 4- d] pyrimidine-2, 5-dione derivatives and their use as human neutrophil elastase inhibitors |
| WO2009060206A1 (en) | 2007-11-07 | 2009-05-14 | Argenta Discovery Limited | 3,4,6,7-tetrahydro-1h-pyrrolo[3,4-d]pyrimidine-2,5-diones and their therapeutic use |
| GB0721866D0 (en) | 2007-11-07 | 2007-12-19 | Argenta Discovery Ltd | Pharmaceutical compounds having dual activities |
| DE102008022521A1 (de) | 2008-05-07 | 2009-11-12 | Bayer Schering Pharma Aktiengesellschaft | 1,4-Diaryl-pyrimidopyridazin-2,5-dione und ihre Verwendung |
| DE102007061766A1 (de) | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | 4-(4-Cyano-2-thioaryl)-dihydropyrimidinone und ihre Verwendung |
| MY150285A (en) * | 2007-12-20 | 2013-12-31 | Bayer Ip Gmbh | 4-(4-cyano-2-thioaryl)dihydropyrimidinones and their use |
| DE102009004197A1 (de) | 2009-01-09 | 2010-07-15 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch anellierte Diaryldihydropyrimidin-Derivate und ihre Verwendung |
| DE102009016553A1 (de) | 2009-04-06 | 2010-10-07 | Bayer Schering Pharma Aktiengesellschaft | Sulfonamid- und Sulfoximin-substituierte Diaryldihydropyrimidinone und ihre Verwendung |
| GB201004179D0 (en) | 2010-03-12 | 2010-04-28 | Pulmagen Therapeutics Inflamma | Enzyme inhibitors |
| GB201004178D0 (en) | 2010-03-12 | 2010-04-28 | Pulmagen Therapeutics Inflamma | Enzyme inhibitors |
| JP2013177318A (ja) | 2010-06-30 | 2013-09-09 | Dainippon Sumitomo Pharma Co Ltd | ジヒドロピリミジノン誘導体およびその医薬用途 |
| JP5709999B2 (ja) | 2011-08-01 | 2015-04-30 | 大日本住友製薬株式会社 | ウラシル誘導体およびその医薬用途 |
| AR087841A1 (es) | 2011-09-14 | 2014-04-23 | Chiesi Farma Spa | Derivados de tetrahidrotriazolopirimidina |
| BR112015000507A2 (pt) | 2012-07-12 | 2017-06-27 | Chiesi Farm Spa | inibição de enzimas |
| US20140057926A1 (en) | 2012-08-23 | 2014-02-27 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| US20140057920A1 (en) | 2012-08-23 | 2014-02-27 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| US9102624B2 (en) | 2012-08-23 | 2015-08-11 | Boehringer Ingelheim International Gmbh | Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity |
| CN104507700B (zh) | 2012-08-31 | 2017-01-18 | 惠普发展公司，有限责任合伙企业 | 可印刷介质 |
| US20140221335A1 (en) | 2013-02-06 | 2014-08-07 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9198215B2 (en) * | 2013-03-01 | 2015-11-24 | Qualcomm Incorporated | Peer connectivity using reciprocal wireless connections |
| US9115093B2 (en) * | 2013-03-04 | 2015-08-25 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
-
2015
- 2015-07-27 US US14/809,311 patent/US9440930B2/en active Active
- 2015-07-30 WO PCT/EP2015/067506 patent/WO2016016368A1/en active Application Filing
- 2015-07-30 JP JP2017505234A patent/JP6484327B2/ja active Active
- 2015-07-30 EP EP15744232.8A patent/EP3174862B1/en active Active
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